Dehalogenation of Dichlorobenzoates by Acidovorax sp. KKS102’s beta class Glutathione S-transferase and its Mutants

Glutathione s-transferases (GSTs) are ubiquitous family of enzymes well known for their detoxification function. Several different classes of the enzyme exist with beta class being the one specific to bacteria. Recently, the enzymes were found to exhibit other functions, in particular dehalogenation of some organic compounds. This property could be extremely useful especially in the bioremediation of some organochlorine pollutants. A beta class GST from Acidovorax sp. KKS102 designated as KKS-BphK was previously cloned and characterized. In this research, molecular docking study was first employed to investigate the possibility of binding of the protein to dichlorobenzoates; byproducts of polychlorobiphenyl degradation. The wild type enzyme together with other mutants were expressed using E. coli BL21 (DE3) cells and purified. The dehalogenation function of the enzymes against dichlorobenzoate derivatives was also investigated through chloride ion detection assay. The results of the molecular docking study indicated the possibility of binding of KKS-BphK to these substrates. Both the wild type and the mutants showed dehalogenation function against the model substrate 1-chloro-2,4- dinitrobenzene (CDNB). Furthermore, the enzymes also showed dehalogenation function against 2,4-dichlorobenzoate derivatives. However, in testing the activity of the enzymes toward 2,5- dichlorobenoate and 2,6-dichlorobenzoate, only K107T and A180P mutants showed some activity while the wild type and C10F mutant showed zero activity. The research indicates the usefulness of beta class GST in the dehalogenation of dichlorobenzoates in addition to their known function of dehalogenating monochlorobenzoates. Keywords: Glutathione s-transferase, Mutants, Beta class, dehalogenation, dichlorobenzoates.

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In-silico Investigation of the Interaction between Beta-class Glutathione S-Transferase and Five Antibiotics, namely; Ampicillin, Tetracycline, Chloramphenicol, Ciprofloxacin and Cephalexin

Journal of Applied Sciences and Environmental Management ◽

10.4314/jasem.v25i4.2 ◽

2021 ◽

Vol 25 (4) ◽

pp. 497-502

Author(s):

D. Shehu ◽

S Danlami ◽

M. Ya’u ◽

A. Babandi ◽

H.M. Yakasai ◽

...

Keyword(s):

Amino Acids ◽

Antibiotic Resistance ◽

Molecular Docking ◽

Binding Site ◽

Substrate Binding ◽

Docking Study ◽

Glutathione S Transferase ◽

Molecular Docking Study ◽

Substrate Binding Site ◽

Glutathione S Transferases

Glutathione s-transferases(GSTs) are enzymes involved in the conjugation and deactivation of various xenobiotics including drugs. Thisin-silico study was undertaken in order to investigate the interaction between beta-class glutathione s-transferase and five selected antibiotics, namely; ampicillin, tetracycline, chloramphenicol, ciprofloxacin and cephalexin using molecular docking study. RaptorX server was used to predict the amino acids involved at the binding sitewhile molecular docking study was employed in order to investigate the binding interactions.RaptorX predicted several amino acids which were different from the ones observed in molecular docking because of the variability in the substrate binding site of GSTs however, all the amino acids predicted by RaptorX were also found to be involved in the GSH binding.Lys107, Phe109, Ser110, Leu113, Trp114, His115 and Arg123, Leu168 were the amino acids involved in the binding of various antibiotics to the substrate binding site of the protein while Ala9, Cys10, Leu32, Tyr51, Val52, Pro53, Glu65 and Ala66were involved in the binding of the co-substrate GSH to the binding site of the protein. The results indicated that all the antibiotics showed a good binding affinity with the beta class GST and are therefore capable of deactivating the drugs. With these, finding a beta class GST inhibitors alongside antibiotics during a treatment of diseases will be of beneficial in the current fight against antibiotic resistance.

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Screening for novel lead compounds targeting benzodiazepine allosteric binding site of wild-type and H129Y variant of GABAA receptor: an in-silico molecular docking study

International Journal of Computational Biology and Drug Design ◽

10.1504/ijcbdd.2021.10042525 ◽

2021 ◽

Vol 14 (5) ◽

pp. 1

Author(s):

Naresh Krishna Narasimha ◽

Sai Manohar Thota

Keyword(s):

Molecular Docking ◽

Binding Site ◽

Gabaa Receptor ◽

In Silico ◽

Docking Study ◽

Wild Type ◽

Molecular Docking Study ◽

Lead Compounds ◽

In Silico Molecular Docking

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Design and optimization of N-acylhydrazone pyrimidine derivatives as E. coli PDHc E1 inhibitors: Structure-activity relationship analysis, biological evaluation and molecular docking study

Bioorganic & Medicinal Chemistry ◽

10.1016/j.bmc.2017.08.038 ◽

2017 ◽

Vol 25 (20) ◽

pp. 5652-5661 ◽

Cited By ~ 9

Author(s):

Haifeng He ◽

Hongying Xia ◽

Qin Xia ◽

Yanliang Ren ◽

Hongwu He

Keyword(s):

Molecular Docking ◽

Docking Study ◽

Biological Evaluation ◽

Activity Relationship ◽

Pyrimidine Derivatives ◽

Molecular Docking Study ◽

Design And Optimization ◽

E Coli ◽

Relationship Analysis ◽

Structure Activity

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Development of Multi-concentration Cu:Ag Bimetallic Nanoparticles as a Promising Bactericidal for Antibiotic-Resistant Bacteria as Evaluated with Molecular Docking Study

Nanoscale Research Letters ◽

10.1186/s11671-021-03547-6 ◽

2021 ◽

Vol 16 (1) ◽

Author(s):

Shumaila Mureed ◽

Sadia Naz ◽

Ali Haider ◽

Ali Raza ◽

Anwar Ul-Hamid ◽

...

Keyword(s):

Molecular Docking ◽

Biosynthetic Pathway ◽

Bimetallic Nanoparticles ◽

Docking Study ◽

Resistant Bacteria ◽

Antibiotic Resistant Bacteria ◽

Molecular Docking Study ◽

Antibiotic Resistant ◽

E Coli ◽

Binding Score

AbstractThe present study is concerned with evaluating the influence of various concentrations of Ag within Cu:Ag bimetallic nanoparticles developed for use as a promising anti-bacterial agent against antibiotic-resistant bacteria. Here, Cu:Ag bimetallic nanoparticles with various concentration ratios (2.5, 5.0, 7.5, and 10 wt%) of Ag in fixed amount of Cu labeled as 1:0.025, 1:0.050, 1:0.075, and 1:0.1 were synthesized using co-precipitation method with ammonium hydroxide and deionized water as solvent, polyvinyl pyrrolidone as a capping agent, and sodium borohydride and ascorbic acid as reducing agents. These formulated products were characterized through a variety of techniques. XRD confirmed phase purity and detected the presence of distinct fcc structures belonging to Cu and Ag phases. FTIR spectroscopy confirmed the presence of vibrational modes corresponding to various functional groups and recorded characteristic peak emanating from the bimetallic. UV–visible spectroscopy revealed reduction in band gap with increasing Ag content. SEM and HR-TEM micrographs revealed spherical morphology of Ag-doped Cu bimetallic with small and large scale agglomerations. The samples exhibited varying dimensions and interlayer spacing. Bactericidal action of synthesized Cu:Ag bimetallic NPs depicted statistically significant (P < 0.05) inhibition zones recorded for various concentrations of Ag dopant against Staphylococcus aureus (S. aureus), Escherichia coli (E. coli), and Acinetobacter baumannii (A. baumannii) ranging from (0.85–2.8 mm), (0.55–1.95 mm) and (0.65–1.85 mm), respectively. Broadly, Cu:Ag bimetallic NPs were found to be more potent against gram-positive compared with gram-negative. Molecular docking study of Ag–Cu bimetallic NPs was performed against β-lactamase which is a key enzyme of cell wall biosynthetic pathway from both S. aureus (Binding score: − 4.981 kcal/mol) and A. bauminnii (Binding score: − 4.013 kcal/mol). Similarly, binding interaction analysis against FabI belonging to fatty acid biosynthetic pathway from A. bauminnii (Binding score: − 3.385 kcal/mol) and S. aureus (Binding score: − 3.012 kcal/mol) along with FabH from E. coli (Binding score: − 4.372 kcal/mol) was undertaken. These theoretical computations indicate Cu-Ag bimetallic NPs as possible inhibitor of selected enzymes. It is suggested that exploring in vitro inhibition potential of these materials may open new avenues for antibiotic discovery.

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Rational Synthesis of Some New para-Aminobenzoic Acid Hybrids with Thiazolidin-2,4-diones with Antimicrobial Properties. ADMET and molecular docking evaluation

Revista de Chimie ◽

10.37358/rc.19.3.7004 ◽

2019 ◽

Vol 70 (3) ◽

pp. 769-775 ◽

Cited By ~ 1

Author(s):

Gabriel Marc ◽

Smaranda Oniga ◽

Adrian Pirnau ◽

Mihaela Duma ◽

Laurian Vlase ◽

...

Keyword(s):

Antimicrobial Activity ◽

Molecular Docking ◽

Physicochemical Characterization ◽

Antimicrobial Properties ◽

Docking Study ◽

Aminobenzoic Acid ◽

Molecular Docking Study ◽

E Coli ◽

Activity Screening

The present paper presents the synthesis, physicochemical characterization, in vitro antimicrobial activity and the molecular docking study of a series of ten new thiazolidine-2,4-dione derivatives conjugated to para-aminobenzoic acid (PABA). The lipophilicity of the new molecules was evaluated in silico. Quantitative elemental C, H, N, S analysis and spectral data (mass spectrometry, infrared and nuclear magnetic resonance) were consistent with the expected data. The results of the antimicrobial activity screening revealed that some of the synthesized compounds had moderate to good activity against E. coli ATCC 25922, S. aureus, ATCC 6538P and C. albicans ATCC 10231.

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